Identification and Isolation of Components from the Venom of the Snail Conus distans which Target the Somatostatin Receptor

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Abstract

This study reports two partially isolated agonists or antagonists for somatostatin
from the toxin of the marine snail, Conus distans. Somatostatin is a widely distributed
hormone that has five receptor Subtypes, and, to date, it does not have any known
antagonists or selective agonists for all receptor Subtypes. (Reisine and Bell, 1995) The
venoms from thirteen species of Cone snails were examined in an assay for somatostatin
receptor-site competition using radiolabeled 125 I-Tyr 11-somatostatin and a whole rat brain
tissue preparation. Our results show that the venom from Conus distans completely
inhibits binding of somatostatin. The venoms from other Cone snail species gave only
partial or no inhibition of selective somatostatin binding in this assay. A series of
sequential separations by reverse-phase HPLC, monitored by somatostatin binding assays
were then used to partially purify the active material in the Conus distans venom. A
procedure to differentiate somatostatin agonist or antagonist activity was developed in this
project based on the agonist-stimulated GTP[y-35 S] binding assay in membranes (Sim et
aI., 1995). To employ this assay, we first established that somatostatin stimulates GTP
binding to the G-protein in this assay. Somatostatin had not previously been shown to
stimulate GTP binding in this assay. Future work using this assay will be necessary to
determine if the active material from the Conus distans venom is an agonist or antagonist
of somatostatin stimulation of GTP binding to G-proteins. Development of selective
somatostatin agonists and antagonists will be useful in the characterization of somatostatin
receptors and may be clinically useful in the treatment of central nervous system (CNS)
abnormalities related to somatostatin such as motor disorders, Alzheimer's disease, and
epilepsy (Epelbaum, 1986; Raynor and Reisine, 1992; Reisine and Bell, 1995).